Native Ancestry Research Articles

The EAT-Lancet Diet Index Is Associated with Lower Obesity and Incidence of Type 2 Diabetes in the Multiethnic Cohort

BackgroundThe EAT-Lancet Commission has developed dietary recommendations, named the EAT-Lancet diet, to promote healthy nutrition and sustainable food production worldwide. ObjectivesWe developed an adapted score for the EAT-Lancet diet for participants of the Multiethnic Cohort (MEC) Study and its relation with incidence of obesity and type 2 diabetes (T2D). MethodsThe MEC includes 5 ethnic groups followed since 1993–1996. Anthropometric characteristics and dietary intake were assessed by questionnaire at cohort entry (Qx1) and 10 y later (Qx3). To create the EAT-Lancet index (range: 0–48 points), a 3-point scoring system for 16 food groups standardized to 2500 kcal/d was applied. T2D cases were identified through repeated self-reports and administrative data. In a prospective design, obesity at Qx3 and T2D incidence were evaluated using Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) while adjusting for relevant covariates. ResultsAmong 193,379 MEC participants, the overall mean of the EAT-Lancet index score was 25 ± 4 points and 46,140 new T2D cases were identified. Higher adjusted means were observed in females than males, in participants of Japanese American and Native Hawaiian ancestry, and in those with healthy weight than overweight or obese. Obesity was lower in cohort members with higher EAT-Lancet scores (HR: 0.76; 95% CI: 0.73, 0.79 for tertile 3 compared with 1). Although T2D incidence was 10% lower among participants in the highest (27–42 points) compared with the lowest (9–23 points) EAT-Lancet index tertile (HR: 0.90; 95% CI: 0.88, 0.92), the association was attenuated after BMI adjustment (HR: 0.97; 95% CI: 0.94, 0.99). This inverse association with T2D was restricted to African American and European American participants. ConclusionsThese findings support the hypothesis that adherence to the EAT-Lancet diet is related to a lower risk of obesity, which may be partially responsible for the small reduction in T2D incidence.

Pharmacogenomic implications of the differential distribution of CYP3A5 metabolic phenotypes among Latin American populations.

This study shows that the distribution of CYP3A5 alleles (*1, *3, *6 and *7) and genotype-predicted CYP3A5 phenotypes vary significantly across Latin American cohorts (Brazilians and the One Thousand Genomes Admixed American superpopulation), as well as among subcohorts comprising individuals with the highest proportions of Native, European or sub-Saharan African ancestry. Differences in biogeographical ancestry across the study groups are the likely explanation for these results. The differential distribution of CYP3A5 phenotypes has major pharmacogenomic implications, affecting the proportion of individuals carrying high risk CYP3A5 phenotypes for the immunosuppressant tacrolimus and the number of patients that would need to be genotyped to prevent acute rejection in kidney transplant recipients under tacrolimus treatment.

Association of APOE with Alzheimer’s disease in Mexico, Caribbean‐Hispanics, Peruvian and Mexican Americans

AbstractBackgroundThe Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Late Onset Alzheimer’s disease (LOAD). However, its genetic effect is heterogeneous across different ethnicities. We investigated the association of APOE with LOAD in five different Hispanic studies: Mexicans in the Mexican Health and Aging Study (MHAS), Caribbean Hispanics in the Washington Heights Inwood Aging project (WHICAP), Peruvians in the Genetics of Alzheimer’s disease In Peruvian Populations (GAPP) and Mexican Americans from The Health & Aging Brain among Latino Elders (HABLE) and the Texas Alzheimer’s Research and Care Consortium (TARCC).MethodA total of 7,832 participants were included in the analysis. APOE genotypes were generated by direct genotyping or imputation. SNPs associations with LOAD were assessed using multivariate logistic regression models in PLINK. Analyses were adjusted for age (≥60 years old), sex, and education. Global ancestry proportions, Native Americans, European, African were estimated with ADMIXTURE software using the Human Genome Diversity Project as the reference panel. Genetic ancestry specific secondary analyses were conducted using the same models.ResultThe genetic ancestral composition was significantly different across cohorts. Peruvians and Mexicans showed a predominant native ancestry, Caribbean‐Hispanics appeared to have a major contribution of European ancestry, and Mexican Americans exhibited similar proportions of both European and Native ancestries. We observed a significant association with e4 allele dosage in all the cohorts, except for MHAS. The genetic effect of at least one copy of the e4 allele on LOAD risk was very similar in GAPP and HABLE (OR = 3.42, SE = 0.39 and OR = 3.33, SE = 0.33, respectively), while attenuated in TARCC (OR = 2.81, SE = 0.28) and WHICAP (OR = 1.82, SE = 0.16). Among MHAS participants with a predominant European ancestry, APOE association achieved statistical significance with an increased disease risk (OR = 3.42, SE = 0.55) for homozygous carriers. Within the native‐prevalent ancestry subsample, the increased LOAD risk among APOE_ e4 heterozygous carriers were similar in both GAPP and HABLE cohorts (OR = 3.61, SE = 0.44 and OR = 3.64, SE = 0.43, respectively).ConclusionOur results showed a differential risk for LOAD from the APOE_ e4 allele across populations with admixed genetic ancestry.

A review of ancestrality and admixture in Latin America and the caribbean focusing on native American and African descendant populations.

Genomics can reveal essential features about the demographic evolution of a population that may not be apparent from historical elements. In recent years, there has been a significant increase in the number of studies applying genomic epidemiological approaches to understand the genetic structure and diversity of human populations in the context of demographic history and for implementing precision medicine. These efforts have traditionally been applied predominantly to populations of European origin. More recently, initiatives in the United States and Africa are including more diverse populations, establishing new horizons for research in human populations with African and/or Native ancestries. Still, even in the most recent projects, the under-representation of genomic data from Latin America and the Caribbean (LAC) is remarkable. In addition, because the region presents the most recent global miscegenation, genomics data from LAC may add relevant information to understand population admixture better. Admixture in LAC started during the colonial period, in the 15th century, with intense miscegenation between European settlers, mainly from Portugal and Spain, with local indigenous and sub-Saharan Africans brought through the slave trade. Since, there are descendants of formerly enslaved and Native American populations in the LAC territory; they are considered vulnerable populations because of their history and current living conditions. In this context, studying LAC Native American and African descendant populations is important for several reasons. First, studying human populations from different origins makes it possible to understand the diversity of the human genome better. Second, it also has an immediate application to these populations, such as empowering communities with the knowledge of their ancestral origins. Furthermore, because knowledge of the population genomic structure is an essential requirement for implementing genomic medicine and precision health practices, population genomics studies may ensure that these communities have access to genomic information for risk assessment, prevention, and the delivery of optimized treatment; thus, helping to reduce inequalities in the Western Hemisphere. Hoping to set the stage for future studies, we review different aspects related to genetic and genomic research in vulnerable populations from LAC countries.

How are people with orofacial clefts attended in northwest region of São Paulo state, Brazil?

Characterization of specific birth defects is essential for conducting scientific investigations, care and therapeutic strategies. This article describes demographic, clinical and genetic aspects, risk factors and access to treatment of Brazilian patients with orofacial clefts registered in a specialized collaborative center of the Brazilian Database on Craniofacial Anomalies (BDCA). We interviewed 70 individuals with typical orofacial clefts using a standard instrument from the database and subjected them to genetic testing. The patients were grouped as syndromic and non-syndromic. The majority of individuals were of lower middle class, native ancestry and syndromic. There was a significant difference in the type of clefts regarding gender. There was no significant difference between bilateral and unilateral, between the side affected, right and left, or familial recurrence related to type of oral cleft. The risk factor familial recurrence was significantly higher among non-syndromic cases. Etiological factors were identified or suggested in 62.5% of the syndromic cases. There was a delay in diagnosis and in access to treatment in most cases. We concluded that gender, native ancestry and low family income represent risk factors. Furthermore, the distribution by cleft types and gender is similar to previous studies. The results can guide scientific investigations and care policies.

Pioneer Mother

Pioneer Mother

Higher native Peruvian genetic ancestry proportion is associated with tuberculosis progression risk

SUMMARYWe investigated whether ancestry-specific genetic factors affect tuberculosis (TB) progression risk in a cohort of admixed Peruvians. We genotyped 2,105 patients with TB and 1,320 household contacts (HHCs) who were infected with Mycobacterium tuberculosis (M. tb) but did not develop TB and inferred each individual’s proportion of native Peruvian genetic ancestry. Our HHC study design and our data on potential confounders allowed us to demonstrate increased risk independent of socioeconomic factors. A 10% increase in individual-level native Peruvian genetic ancestry proportion corresponded to a 25% increased TB progression risk. This corresponds to a 3-fold increased risk for individuals in the highest decile of native Peruvian genetic ancestry versus the lowest decile, making native Peruvian genetic ancestry comparable in effect to clinical factors such as diabetes. Our results suggest that genetic ancestry is a major contributor to TB progression risk and highlight the value of including diverse populations in host genetic studies.

The Health of Immigrant Youth in Denmark: Examining Immigrant Generations and Origin

First-generation migrants tend to have better health than those of native ancestry, while second-generation migrants often are affected by negative health assimilation. Less is known about immigrants arriving before their teens, the 1.5 generation, or those with one native and one immigrant parent, the 2.5 generation. We apply logistic regression models to study physical and mental health outcomes for immigrant youth across generations using Danish register data. We take heterogeneities into account studying gender and origin differences. Our analysis shows that first- and 1.5-generation immigrants have better physical health than natives, while the physical health of the second and 2.5 generations is the same or worse than natives. For mental health, the 2.5 generation is the only group with worse outcomes than natives, which we relate to identification struggles translating into poorer mental health. When studying potential heterogeneities, we find that males belonging to the second generation with an African background have a higher likelihood of hospitalization for a mental health issue.

Uveitis Patterns and Severity: An Epidemiologic Study from a Tertiary Care Private Referral Center in Buenos Aires, Argentina

ABSTRACT Purpose To report uveitis’ spectrum in a private practice cohort in the city of Buenos Aires, Argentina. Methods Retrospective review at Instituto de la Visión (November 2011-October 2015). Standard demographics, ethnicity and Native American aboriginal ancestry were recorded. Results Among 212 patients, median age 45 (6-97), 10% pediatric, 35% bilateral, 72% non-idiopathic, 36% infectious. Anterior uveitis presented in 50%, followed by posterior (32%), intermediate (9%) and panuveitis (8%). Frequent visits (≥ 6 per year) needed by 29%: posterior, non-idiopathic disease with 79% systemic immunosuppression requirement was their main presentation. Native American aboriginal ancestry was reported by 22.64% of the whole cohort and 37% of frequent visits’ subgroup. Conclusions Unilateral, non-idiopathic, non-infectious anterior uveitis was the most frequent presentation, in agreement with reports coming from western developed cities. The multi-racial Argentinian population with specific Native American aboriginal ancestry might contribute to certain forms of posterior uveitis and their response to treatment.

Subsequent risk of suicide among 9,300,812 cancer survivors in US: A population-based cohort study covering 40 years of data.

SummaryBackgroundLarge cohort studies that estimate the variation in suicide risk among cancer patients, depending on disease type and patient characteristics, are lacking. We aimed to investigate suicide risk among patients with different cancers types in the United States (US) and to identify subsets of patients at particularly high risk.MethodsA total of 9,300,812 cases of cancer in the Surveillance, Epidemiology, and End Results (SEER) database that were diagnosed between 1975 and 2016 were included in the study. Standardized mortality ratio (SMR) and absolute excess risk (AER) of suicide were estimated.FindingsFrom the included cases, 14,423 cancer patients were identified as having died by suicide, representing 0.26% of all deaths. We found that cancer patients had a higher risk of suicide compared with the general population, which equated to 0.8 excess deaths per 10,000 person-years. Greater suicide risk was correlated with the following: specific cancer sites, male sex, American Indian/Alaskan Native ancestry, being divorced, being uninsured, distance of metastasis, aged between 60 and 69 at diagnosis, and having a more recent diagnosis. The greatest SMR and AER were found in patients with cancers of the respiratory system, followed by those of the oral cavity and pharynx, myeloma, bones and joints, digestive system, and brain and other nervous system cancers.InterpretationSuicide risk among cancer patients varies greatly and depends on both disease type and patient characteristics. A tailored clinical management should be considered for patients at a higher risk of suicide.FundingNatural Science Foundation of China.

The Ancestry of Eastern Paraguay: A Typical South American Profile with a Unique Pattern of Admixture.

Immigrants from diverse origins have arrived in Paraguay and produced important demographic changes in a territory initially inhabited by indigenous Guarani. Few studies have been performed to estimate the proportion of Native ancestry that is still preserved in Paraguay and the role of females and males in admixture processes. Therefore, 548 individuals from eastern Paraguay were genotyped for three marker sets: mtDNA, Y-SNPs and autosomal AIM-InDels. A genetic homogeneity was found between departments for each set of markers, supported by the demographic data collected, which showed that only 43% of the individuals have the same birthplace as their parents. The results show a sex-biased intermarriage, with higher maternal than paternal Native American ancestry. Within the native mtDNA lineages in Paraguay (87.2% of the total), most haplogroups have a broad distribution across the subcontinent, and only few are concentrated around the Paraná River basin. The frequency distribution of the European paternal lineages in Paraguay (92.2% of the total) showed a major contribution from the Iberian region. In addition to the remaining legacy of the colonial period, the joint analysis of the different types of markers included in this study revealed the impact of post-war migrations on the current genetic background of Paraguay.

Connecticut State Library Spotlight

Connecticut State Library Spotlight

Development of Genetic Baseline Information to Support the Conservation and Management of Wild Brook Trout in North Carolina

AbstractAfter centuries of declines, there is growing interest in conserving extant wild populations of Brook Trout Salvelinus fontinalis and reintroducing Brook Trout populations of native ancestry. A population genetic baseline can enhance conservation outcomes and promote restoration success. Consequently, it is important to document existing patterns of genetic variation across the landscape and translate these data into an approachable format for fisheries managers. We genotyped 9,507 Brook Trout representing 467 wild collections at 12 microsatellite loci to establish a genetic baseline for North Carolina, USA. Rarefied allelic richness (mean = 3.12) and observed heterozygosity (mean = 0.42), which reflect within‐population diversity, were low to moderate relative to levels typically observed at higher latitudes. Effective population sizes (Ne) varied widely but were often very low (151 collections had an estimated Ne < 10). Despite decades of intensive stocking across the state, we found little to no evidence of hatchery introgression in most populations. Although genetic variation was significant at a variety of spatial scales (mean pairwise = 0.73), substantial genetic variation occurred between patches within individual watersheds. Analysis of molecular variance indicated that a substantial portion (28.5%) of the observed genetic variation was attributable to differences among populations, with additional genetic variation among hydrologic unit codes (HUCs; 16.0, 16.6, 12.1, and 9.4% of the overall variation among 12‐, 10‐, 8‐, and 6‐digit HUCs, respectively). We discuss a suite of potential applications for this type of genetic data to enhance management outcomes, such as conservation prioritization and selection of source stocks for reintroductions or genetic rescue.

Abstract P629: Genome-Wide Association Study of Individuals of Native Hawaiian Ancestry Reveals Unique Genetic Risk Factors for Stroke and Myocardial Infarction

Background: Several genetic susceptibility risk loci for ischemic stroke have been identified. However, the relative dearth of genetic data from populations of non-European ancestry has the potential to create disparities in access to genomics-based precision medicine strategies. Individuals of Native Hawaiian ancestry represent a particularly understudied group in stroke genomics research despite facing high rates of cerebrovascular disease. Hypothesis: Genetic variants associated with stroke differ between Native Hawaiians and previously studied groups of predominantly European ancestry. Methods: We conducted a genome-wide (GW) association study of stroke and myocardial infarction (MI) in an adult population of Native Hawaiian ancestry, using data from the Multiethnic Cohort study (MEC). Genetic information was ascertained via genome-wide array genotyping using the AB OpenArray and TaqMan platforms followed by imputation to 1000 Genomes reference panels. We pursued replication of variants that were GW significant (p<5x10 -8 ) or yielded suggestive associations (p<5x10 -7 ) in the prior stroke GW association study MEGASTROKE. Results: We identified 2,104 individuals (1,089 [51.8%] female) of Native Hawaiian ancestry, including 173 cases and 1,931 controls. We identified one novel susceptibility risk locus at a narrow intronic region located at chromosome q26.2 (top associated SNP 3:169096251, OR 2.48, 95%CI 1.81-3.41; p=1.93x10 -8 ), overlying the MECOM gene. We also identified 9 other suggestive risk loci at p<5x10 -7 . When replicating in MEGASTROKE, q26.2 did not have available counterpart variants to analyze, and 3 out of 9 suggestive signals were associated with ischemic stroke subtypes at p<0.05. Conclusions: We report the first GW association study of ischemic stroke and myocardial infarction in a Native Hawaiian population. We identified one susceptibility risk locus at q26.2, located in a narrow intronic region of MECOM, a gene that codes for a histone-lysine N-methyltransferase that has transcriptional regulation and oncoprotein functions. The lack of available replication data for this locus in the large MEGASTROKE collaboration emphasizes the importance of developing genomic resources across ancestral groups.

The impact of global and local Polynesian genetic ancestry on complex traits in Native Hawaiians.

Epidemiological studies of obesity, Type-2 diabetes (T2D), cardiovascular diseases and several common cancers have revealed an increased risk in Native Hawaiians compared to European- or Asian-Americans living in the Hawaiian islands. However, there remains a gap in our understanding of the genetic factors that affect the health of Native Hawaiians. To fill this gap, we studied the genetic risk factors at both the chromosomal and sub-chromosomal scales using genome-wide SNP array data on ~4,000 Native Hawaiians from the Multiethnic Cohort. We estimated the genomic proportion of Native Hawaiian ancestry (“global ancestry,” which we presumed to be Polynesian in origin), as well as this ancestral component along each chromosome (“local ancestry”) and tested their respective association with binary and quantitative cardiometabolic traits. After attempting to adjust for non-genetic covariates evaluated through questionnaires, we found that per 10% increase in global Polynesian genetic ancestry, there is a respective 8.6%, and 11.0% increase in the odds of being diabetic (P = 1.65×10−4) and having heart failure (P = 2.18×10−4), as well as a 0.059 s.d. increase in BMI (P = 1.04×10−10). When testing the association of local Polynesian ancestry with risk of disease or biomarkers, we identified a chr6 region associated with T2D. This association was driven by an uniquely prevalent variant in Polynesian ancestry individuals. However, we could not replicate this finding in an independent Polynesian cohort from Samoa due to the small sample size of the replication cohort. In conclusion, we showed that Polynesian ancestry, which likely capture both genetic and lifestyle risk factors, is associated with an increased risk of obesity, Type-2 diabetes, and heart failure, and that larger cohorts of Polynesian ancestry individuals will be needed to replicate the putative association on chr6 with T2D.

The ghosts of propagation past: haplotype information clarifies the relative influence of stocking history and phylogeographic processes on contemporary population structure of walleye (Sander vitreus).

Stocking of fish is an important tool for maintaining fisheries but can also significantly alter population genetic structure and erode the portfolio of within‐species diversity that is important for promoting resilience and adaptability. Walleye (Sander vitreus) are a highly valued sportfish in the midwestern United States, a region characterized by postglacial recolonization from multiple lineages and an extensive history of stocking. We leveraged genomic data and recently developed analytical approaches to explore the population structure of walleye from two midwestern states, Minnesota and Wisconsin. We genotyped 954 walleye from 23 populations at ~20,000 loci using genotyping by sequencing and tested for patterns of population structure with single‐SNP and microhaplotype data. Populations from Minnesota and Wisconsin were highly differentiated from each other, with additional substructure found in each state. Population structure did not consistently adhere to drainage boundaries, as cases of high intra‐drainage and low inter‐drainage differentiation were observed. Low genetic structure was observed between populations from the upper Wisconsin and upper Chippewa river watersheds, which are found as few as 50 km apart and were likely homogenized through historical stocking. Nevertheless, we were able to differentiate these populations using microhaplotype‐based co‐ancestry analysis, providing increased resolution over previous microsatellite studies and our other single SNP‐based analyses. Although our results illustrate that walleye population structure has been influenced by past stocking practices, native ancestry still exists in most populations and walleye populations may be able to purge non‐native alleles and haplotypes in the absence of stocking. Our study is one of the first to use genomic tools to investigate the influence of stocking on population structure in a nonsalmonid fish and outlines a workflow leveraging recently developed analytical methods to improve resolution of complex population structure that will be highly applicable in many species and systems.

Population impact of pharmacogenetic tests in admixed populations across the Americas

The current population of the Americas (~1 billion people) is highly heterogeneous as a result of five centuries of admixture between three major parental populations, namely Native Amerindians, Europeans, and subSaharan Africans. This heterogeneity has important pharmacogenetic (PGx) implications. The present study explores this issue with respect to the population impact of PGx tests listed in the CPIC and DWPG guidelines for the cancer chemotherapeutic agents fluoropyrimidines, irinotecan, and thiopurines. Population impact was assessed by the number of individuals needed to genotype (NNG) and to treat [NNT] in order to prevent one additional adverse effect. The 1000 Genomes Project database was accessed to obtain genotypes for the relevant PGx markers and to estimate individual proportions of Native, European, and African ancestry for six recently admixed populations across the Americas. The ancestry proportions were then employed to devise three sub-cohorts, denoted NAT, EUR, and AFR, in which one of the three major ancestral roots predominates largely (8 to 30-fold) over the other two. Minor allele frequency (MAF) of NUDT15 rs116855232, TPMT rs1800460, and UGT1A1 rs887829 differed significantly across the three sub-cohorts, whereas no difference was observed for TPMT rs1142345 and 1800462, and the four DPYD variants interrogated. The frequency of combined TPMT/NUDT and UGT1A1, but not DPD, metabolic phenotypes differed significantly among the sub-cohorts. The NNGs for the drug/sub-cohorts pairs, ranged from 12 (irinotecan/UGT1A1 in EUR) to 360 (fluoropyrimidines/DPYD in NAT). Differences in MAF of the interrogated variants and consequently in the distribution of metabolic phenotypes, plus the variable individual proportions of biogeographical ancestry concur to the 30-fold range of NNGs for the PGx tests, across the sub-cohorts. This large variation is likely to influence the perceived benefits and the clinical adoption of PGx screening for the chemotherapeutic agents investigated. This is of especial concern for fluoropyrimidines, in view of the large NNGs observed in the study sub-cohorts (NNG = 176-360) and confirmed in cancer patients from Brazil (NNG = 312).

Population-specific genetic background for the OPRM1 variant rs1799971 (118A>G): implications for genomic medicine and functional analysis.

The mu-opioid receptor (MOR, OPRM1) has important roles in diverse functions including reward, addiction, and response to pain treatment. SNP rs1799971 (118A > G, N40D) which occur at a high frequency (40-60%) in Asia and moderate frequency (15%) in samples of European ancestry, is the only common coding variant in the canonical transcript, in non-African populations. Despite extensive studies, the molecular consequences of this variation remained unresolved. The aim of this study was to determine the genetic background of the OPRM1 region of 118G in four representative populations and to assess its potential modulatory effect. Seven common haplotypes with distinct population distribution were identified based on seven SNPs. Three haplotypes carry the 118G and additional highly linked regulatory SNPs (e.g., rs9383689) that could modulate the effect of 118G. Extended analysis in the 1000 Genomes database (n = 2504) revealed a common East Asian-specific haplotype with a different genetic background in which there are no variant alleles for an upstream LD block tagged by the eQTL rs9397171. The major European haplotype specifically includes the eQTL intronic SNP rs62436463 that must have arisen after the split between European and Asian populations. Differentiating between the effect of 118G and these SNPs requires specific experimental approaches. The analysis also revealed a significant increase in two 118A haplotypes with eQTL SNPs associated with drug addiction (rs510769) and obesity (rs9478496) in populations with native Mexican ancestry. Future studies are required to assess the clinical implication of these findings.

The Indian Doctress in the Nineteenth-Century United States: Race, Medicine, and Labor

Abstract This article addresses the robust market in “Indian medicine” that flourished in the nineteenth century—partly due to the influence of urbanization, industrialization, and new technologies of print—and the specific roles that Indian doctresses played in that phenomenon. Indian doctresses in the United States operated at the intersection of cultural values and beliefs regarding womanhood, medicine, and American Indians. Not all of these women were of Native ancestry, but they all mobilized widespread ideas about Native peoples while seeking entrepreneurial success as healers. Using print culture, the author analyzes strategies employed by women who worked as Indian doctresses and patterns of reactions to their efforts. By combining profiles of women who worked as Indian doctresses with popular but not always positive representations of the type, the article offers a kind of composite biography of an occupation. Women from a wide variety of backgrounds fused caregiving skills with popular assumptions—particularly those involving “indigenous anti-modernity”—to make a living. In this way, Indian doctresses also became useful symbolic figures upon whom changing conceptions of race, gender, and class could be projected and debated. The author thus aims to shed new light not only on histories of American medicine but also on the labors of American women and the business of Indian representation during the nineteenth century.

Abstract C034: Differential gene expression according to ancestry in Hispanic/Latina women with luminal B breast cancer

Abstract Background: Breast cancer (BC) is the second leading cause of cancer-related death in women. There is a lack of breast cancer studies showing the differential gene expression in minorities. We have previously found differences in gene expression according to ancestry in Hispanic/Latina women with BC. The goal of our study was to determine the differential gene expression between high and low European, African, and Native ancestries of Hispanic/Latina women with luminal B BC. Methods: Breast cancer tissue samples were collected from the Moffitt Cancer Center (MCC) in Tampa, FL, and had been analyzed for ancestry informative markers (AIMs) as part of a collaboration between MCC and the University of Puerto Rico. The RNA was quantified, qualified, and used to prepare genomic libraries using regents and protocols from Illumina at the Translational Genomics Core, Stanley S. Scott Cancer Center, LSUHSC-New Orleans. Quality assessment showed close to 50% alignment in coding regions. Raw counts were normalized and used to perform differential gene expression analysis (p<0.05 and fold change >2.0) using DESeq2 in R-Studio between individuals with high and low European, African, and Native ancestral fractions. Heatmaps were used to compare the distribution of the samples visually based on ancestry fraction and the level of gene expression. We used the online tool Venny (http://bioinfogp.cnb.csic.es/tools/venny/) to identify significantly different genes that were uniquely expressed in each ancestral group or shared between them. In addition, we used online tools (http://xcell.ucsf.edu/) for cell infiltration analysis and the software MetaCore to identify possible pathways in which the differentially expressed genes may be involved. Results: We found a significant inverse correlation between European and both African and Native American ancestries, and these clearly separated based on high and low ancestral fraction. Eighteen genes were shared between European and Native American ancestries, showing opposite expression between the ancestries, suggesting an ethnicity-associated expression. The expression of these genes was validated by real-time PCR. Interestingly, cBioportal analysis showed that ANO1, EPN3, PLAT, and TRPA1 genes are frequently amplified in breast cancer. Furthermore, one gene SPAG6 was commonly expressed among all ancestries with a positive correlation in Native ancestry and negative correlation in European ancestry. We found that African ancestry was associated with the infiltration on lymphocyte progenitors and type 2 macrophages. Meanwhile, European and Native ancestries correlated with type 2 lymphocytes and monocytes, respectively. Pathway analysis revealed possible activation of immune responses driven by genes significant in European and Native ancestries. Conclusions: Overall, our data suggest that patients with luminal B breast cancer may have differential gene expression associated to ancestry, to gene abnormalities and differential immune responses. Citation Format: Joussette I. Alvarado, Jone Garai, Li Li, Adam J. Boe, Doug Cress, Teresita Antonia, Jamie Teer, Lucio Miele, Jovanny Zabaleta. Differential gene expression according to ancestry in Hispanic/Latina women with luminal B breast cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C034.